Wilson Harry, Macdonald Douglas, Bryce Kathleen
Hepatology Department, Royal Free Hospital, London, UK.
Insitute for Global Health, University College London University, London, UK.
Case Rep Gastroenterol. 2024 Jun 27;18(1):347-351. doi: 10.1159/000539646. eCollection 2024 Jan-Dec.
Patients with advanced hepatocellular carcinoma (HCC) have limited treatment options in the context of decompensated cirrhosis. HCC occurs in patients with hepatitis C virus (HCV) infection and cirrhosis at 1-4% per year. Direct-acting antiviral (DAA) efficacy is decreased in the presence of HCC. We present a case where immunotherapy may have resulted in HCV clearance, when DAA therapy had been ineffective. We hypothesise that immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway can reverse T-cell exhaustion and aid in the clearance of chronic HCV.
This case study describes a male in his 40 s identified by a re-engagement initiative for HCV, who had been unaware of his diagnosis. On further investigation he was found to have compensated for liver cirrhosis and HCC. He was treated with HCV DAA therapy (sofosbuvir/velpatasvir) and then systemic immunotherapy for HCC with atezolizumab and bevacizumab, in an attempt to downstage the disease. Hepatitis C therapy did not achieve sustained virological response, with viral relapse after the end of treatment. This, combined with ongoing alcohol use, resulted in hepatic decompensation and cessation of immunotherapy after the fifth cycle. The HCV RNA subsequently became undetectable without further DAA re-treatment.
To our knowledge, this is the first case of HCV clearance after DAA relapse and the timing of this event after immunotherapy suggests a causal link. We hypothesise that this may be due to the reversal of antiviral T-cell exhaustion. This would therefore support further investigation into other chronic viral infections that create tumour associated with immunosuppressive microenvironments.
晚期肝细胞癌（HCC）患者在失代偿期肝硬化的情况下治疗选择有限。丙型肝炎病毒（HCV）感染和肝硬化患者中HCC的年发病率为1%-4%。在存在HCC的情况下，直接抗病毒药物（DAA）的疗效会降低。我们报告了一例在DAA治疗无效时免疫治疗可能导致HCV清除的病例。我们推测，靶向PD-1/PD-L1通路的免疫检查点抑制剂可以逆转T细胞耗竭并有助于清除慢性HCV。
本病例研究描述了一名40多岁的男性，他通过一项针对HCV的重新参与计划被确诊，此前他一直不知道自己的病情。进一步检查发现他患有代偿性肝硬化和HCC。他接受了HCV DAA治疗（索磷布韦/维帕他韦），然后使用阿替利珠单抗和贝伐单抗进行HCC的全身免疫治疗，试图降低疾病分期。丙型肝炎治疗未实现持续病毒学应答，治疗结束后病毒复发。这与持续饮酒相结合，导致肝失代偿，在第五周期后停止免疫治疗。随后，在未进行进一步DAA再治疗的情况下，HCV RNA变得无法检测到。
据我们所知，这是DAA复发后HCV清除的首例病例，免疫治疗后这一事件的发生时间表明存在因果关系。我们推测这可能是由于抗病毒T细胞耗竭的逆转。因此，这将支持对其他导致与免疫抑制微环境相关肿瘤的慢性病毒感染进行进一步研究。
